Regulation Of Tumor Angiogenesis Research Articles

Colorectal Cancer Cell-Derived Extracellular Vesicles Promote Angiogenesis Through JAK/STAT3/VEGFA Signaling.

Angiogenesis plays a crucial role in the growth of colorectal cancer (CRC). Recent studies have identified extracellular vesicles (EVs) in the tumor microenvironment as important mediators of cell-to-cell communication. However, the specific role and mechanisms of CRC-derived EVs in regulating tumor angiogenesis remain to be further investigated. EVs were isolated from the conditioned medium of the CRC cells using ultracentrifugation. We investigated the effects of HT-29-derived EVs on tumor growth and angiogenesis in a subcutaneous HT-29 CRC tumor model in mice. Additionally, we evaluated the impact of HT-29-derived EVs on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). Subsequently, bioinformatics analysis was performed to identify relevant signaling pathways, and pathway inhibitors were used to block the activation of these pathways, aiming to elucidate their roles in angiogenesis. We found that HT-29-derived EVs can promote tumor growth and angiogenesis in vivo, as well as significantly enhance the proliferation, migration, and tube formation of HUVECs. Bioinformatics analysis revealed that HT-29-derived EVs may regulate angiogenesis through the JAK/STAT3 signaling pathway. Specifically, we observed that CRC-derived EVs promoted the phosphorylation of STAT3 (p-STAT3) and the expression of VEGFA in the nucleus of HUVECs. Treatment with the STAT3 inhibitor Stattic reduced the nuclear expression of p-STAT3, which impaired its function as a transcription factor, thereby inhibiting VEGFA expression and the pro-angiogenic effects of CRC-derived EVs. EVs derived from CRC cells promote CRC tumor angiogenesis by regulating VEGFA through the JAK/STAT3 pathway in endothelial cells.

Discovery of antitumor diterpenoids from Casearia graveolens targeting VEGFR-2 to inhibit angiogenesis

Eight novel clerodane diterpenoids (1−8) were isolated from the twigs of Casearia graveolens. Their structures were elucidated through comprehensive nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and electronic circular dichroism (ECD) analyses. In addition to structural determination, surface plasmon resonance (SPR) assays were conducted to investigate molecular interactions, revealing that compound 8 exhibited high affinity for vascular endothelial growth factor receptor 2 (VEGFR2), a key regulator of tumor angiogenesis. Subsequent in vivo experiments demonstrated that compound 8 effectively inhibited angiogenesis and displayed significant antitumor activity by suppressing tumor proliferation and metastasis in zebrafish xenograft models. These findings suggest that compound 8 holds promise as an anticancer lead compound targeting VEGFR-2 to obstruct tumor angiogenesis.

ETHE1 dampens colorectal cancer angiogenesis by promoting TC45 Dephosphorylation of STAT3 to inhibit VEGF-A expression

Angiogenesis is critical for colorectal cancer (CRC) progression, but its mechanisms remain unclear. Here, we reveal that ethylmalonic encephalopathy protein 1 (ETHE1), an essential enzyme in hydrogen sulfide catabolism, inhibits VEGF-A expression and tumor angiogenesis in vitro and in vivo. Moreover, we find that this biological function of ETHE1 depends on the STAT3/VEGF-A pathway. Further investigation demonstrates that ETHE1 promotes the interaction between T cell protein tyrosine phosphatase (TC45) and STAT3, resulting in decreased STAT3 phosphorylation and inhibition of the STAT3 signaling pathway. In clinical samples, we find that ETHE1 is downregulated in CRC and positively correlates with survival outcomes of CRC patients. Meanwhile, the negative correlation of ETHE1 and VEGF-A expression is verified in CRC specimens, and the patients with low ETHE1 and high VEGF-A expression exhibits poorer prognosis. Collectively, our study identifies ETHE1 as a novel regulator of tumor angiogenesis, implying its potential as a prognostic biomarker and promising antiangiogenic target for CRC patients.

Hypoxia as a Target for Combination with Transarterial Chemoembolization in Hepatocellular Carcinoma.

Hypoxia is a hallmark of solid tumors, including hepatocellular carcinoma (HCC). Hypoxia has proven to be involved in multiple tumor biological processes and associated with malignant progression and resistance to therapy. Transarterial chemoembolization (TACE) is a well-established locoregional therapy for patients with unresectable HCC. However, TACE-induced hypoxia regulates tumor angiogenesis, energy metabolism, epithelial-mesenchymal transition (EMT), and immune processes through hypoxia-inducible factor 1 (HIF-1), which may have adverse effects on the therapeutic efficacy of TACE. Hypoxia has emerged as a promising target for combination with TACE in the treatment of HCC. This review summarizes the impact of hypoxia on HCC tumor biology and the adverse effects of TACE-induced hypoxia on its therapeutic efficacy, highlighting the therapeutic potential of hypoxia-targeted therapy in combination with TACE for HCC.

Nucleic acid cancer vaccines targeting tumor related angiogenesis. Could mRNA vaccines constitute a game changer?

Tumor related angiogenesis is an attractive target in cancer therapeutic research due to its crucial role in tumor growth, invasion, and metastasis. Different agents were developed aiming to inhibit this process; however they had limited success. Cancer vaccines could be a promising tool in anti-cancer/anti-angiogenic therapy. Cancer vaccines aim to initiate an immune response against cancer cells upon presentation of tumor antigens which hopefully will result in the eradication of disease and prevention of its recurrence by inducing an efficient and long-lasting immune response. Different vaccine constructs have been developed to achieve this and they could include either protein-based or nucleic acid-based vaccines. Nucleic acid vaccines are simple and relatively easy to produce, with high efficiency and safety, thus prompting a high interest in the field. Different DNA vaccines have been developed to target crucial regulators of tumor angiogenesis. Most of them were successful in pre-clinical studies, mostly when used in combination with other therapeutics, but had limited success in the clinic. Apparently, different tumor evasion mechanisms and reduced immunogenicity still limit the potential of these vaccines and there is plenty of room for improvement. Nowadays, mRNA cancer vaccines are making remarkable progress due to improvements in the manufacturing technology and represent a powerful potential alternative. Apart from their efficiency, mRNA vaccines are simple and cheap to produce, can encompass multiple targets simultaneously, and can be quickly transferred from bench to bedside. mRNA vaccines have already accomplished amazing results in cancer clinical trials, thus ensuring a bright future in the field, although no anti-angiogenic mRNA vaccines have been described yet. This review aims to describe recent advances in anti-angiogenic DNA vaccine therapy and to provide perspectives for use of revolutionary approaches such are mRNA vaccines for anti-angiogenic treatments.

Muscone abrogates breast cancer progression through tumor angiogenic suppression via VEGF/PI3K/Akt/MAPK signaling pathways

BackgroundAngiogenesis strongly reflects poor breast cancer outcome and an important contributor to breast cancer (BC) metastasis; therefore, anti-angiogenic intervention is a potential tool for cancer treatment. However, currently used antibodies against vascular endothelial growth factor A (VEGFA) or inhibitors that target the VEGFA receptor are not effective due to weak penetration and low efficiency. Herein, we assessed the anti-BC angiogenic role of muscone, a natural bioactive musk constituent, and explored possible anti-cancer mechanisms of this compound.MethodsCCK-8, EdU, scratch and Transwell assessments were employed to detect the muscone-mediated regulation of breast cancer (BC) and human umbilical vein endothelial cells (HUVECs) proliferation and migration. Tube formation, matrigel plug assay and zebrafish assay were employed for assessment of regulation of tumor angiogenesis by muscone. In vivo xenograft mouse model was constructed to compare microvessel density (MVD), vascular leakage, vascular maturation and function in muscone-treated or untreated mice. RNA sequencing was performed for gene screening, and Western blot verified the effect of the VEGFA-VEGFR2 pathway on BC angiogenic inhibition by muscone.ResultsBased on our findings, muscone suppressed BC progression via tumor angiogenic inhibition in cellular and animal models. Functionally, muscone inhibited BC cell proliferation and migration as well as tumor cell-conditioned medium-based endothelial cell proliferation and migration. Muscone exhibited a strong suppressive influence on tumor vasculature in cellular and animal models. It abrogated tumor cell growth in a xenograft BC mouse model and minimized tumor microvessel density and hypoxia, and increased vascular wall cell coverage and perfusion. Regarding the mechanism of action, we found that muscone suppressed phosphorylation of members of the VEGF/PI3K/Akt/MAPK axis, and it worked synergistically with a VEGFR2 inhibitor, an Akt inhibitor, and a MAPK inhibitor to further inhibit tube formation.ConclusionOverall, our results demonstrate that muscone may proficiently suppress tumor angiogenesis via modulation of the VEGF/PI3K/Akt/MAPK axis, facilitating its candidacy as a natural small molecule drug for BC treatment.

N-myc downstream–regulated gene 1 can promote vasculogenic mimicry and angiogenesis in urothelial carcinoma

Urothelial carcinoma (UC) of the bladder is a common cause of cancer-related death worldwide. Vasculogenic mimicry (VM) is a process by which the malignant cells can generate vascular-like structures formed of periodic acid–Schiff (PAS) positive/CD31 negative extracellular matrix independent of angiogenesis and thus promotes tumor progression. N-myc downstream–regulated gene 1 (NDRG1) is a protein that can modulate tumor angiogenesis; however, its role in regulating tumor angiogenesis and VM formation has not been previously investigated in UC. This study aims to evaluate the role of intra-tumor microvessel density (MVD) (as a surrogate measure of angiogenesis), VM, and NDRG1 in UC and their correlation with different clinicopathologic features, then assess the correlation between them in UC. Sixty specimens of UC of the bladder were included. PAS-CD31 immunohistochemical double staining method was used to evaluate the intra-tumor MVD and VM. Immunohistochemical expression of NDRG1 was also examined. VM and NDRG1 expression were detected in 41.7% and 83.3% of UC specimens respectively. The mean of intra-tumor MVD, VM area, and NDRG1 was significantly higher in tumors with higher grade, lymphovascular invasion, and higher T stage. NDRG1 expression was positively correlated with MVD and VM. We can suggest that MVD, VM, and NDRG1 may serve as poor prognostic markers for UC. The positive correlation between NDRG1 and both MVD and VM may provide the first evidence that NDRG1 can induce tumor angiogenesis and VM in UC which may offer a novel pathway for further therapeutic strategies.

Diterpenoid tanshinones inhibit gastric cancer angiogenesis through the PI3K/Akt/mTOR signaling pathway

Ethnopharmacological relevanceSalvia miltiorrhiza Bunge is a kind of Chinese herbal medicine known for activating blood circulation and removing blood stasis, with the effect of cooling blood and eliminating carbuncles, and has been proven to have the effect of treating tumors. However, the inhibitory effect of Salvia miltiorrhiza Bunge extracts (Diterpenoid tanshinones) on tumors by inhibiting angiogenesis has not been studied in detail. Aim of the studyThis study aimed to investigate the anti-gastric cancer effect of diterpenoid tanshinones (DT) on angiogenesis, including the therapeutic effects and pathways. Materials and methodsThis experiment utilized network pharmacology was used to identify relevant targets and pathways of Salvia miltiorrhiza Bunge-related components in the treatment of gastric cancer. The effects of DT on the proliferation and migration of human gastric cancer cell line SGC-7901 and human umbilical vein endothelial cell line HUVECs were evaluated, and changes in the expression of angiogenesis-related factors were measured. In vivo, experiments were conducted on nude mice to determine tumor activity, size, immunohistochemistry, and related proteins. ResultsThe findings showed that DT could inhibit the development of gastric cancer by suppressing the proliferation of gastric cancer cells, inducing apoptosis, and inhibiting invasion and metastasis. In addition, the content of angiogenesis-related factors and proteins was significantly altered in DT-affected cells and animals. ConclusionsResults suggest that DT has potential as a therapeutic agent for the treatment of gastric cancer, as it can inhibit tumor growth and angiogenesis. It was also found that DT may affect the expression of the angiogenic factor VEGF through the PI3K/Akt/mTOR pathway, leading to the regulation of tumor angiogenesis. This study provides a new approach to the development of anti-tumor agents and has significant theoretical and clinical implications for the treatment of gastric cancer.

Identification and validation of anoikis-related lncRNAs for prognostic significance and immune microenvironment characterization in ovarian cancer.

Anoikis, a form of apoptotic cell death resulting from inadequate cell-matrix interactions, has been implicated in tumor progression by regulating tumor angiogenesis and metastasis. However, the potential roles of anoikis-related long non-coding RNAs (arlncRNAs) in the tumor microenvironment are not well understood. In this study, five candidate lncRNAs were screened through least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis based on differentially expressed lncRNAs associated with anoikis-related genes (ARGs) from TCGA and GSE40595 datasets. The prognostic accuracy of the risk model was evaluated using Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) analyses revealed significant differences in immune-related hallmarks and signal transduction pathways between the high-risk and low-risk groups. Additionally, immune infiltrate analysis showed significant differences in the distribution of macrophages M2, follicular T helper cells, plasma cells, and neutrophils between the two risk groups. Lastly, silencing the expression of PRR34_AS1 and SPAG5_AS1 significantly increased anoikis-induced cell death in ovarian cancer cells. In conclusion, our study constructed a risk model that can predict clinicopathological features, tumor microenvironment characteristics, and prognosis of ovarian cancer patients. The immune-related pathways identified in this study may offer new treatment strategies for ovarian cancer.

Assessing angiogenesis factors as prognostic biomarkers in breast cancer patients and their association with clinicopathological factors

Introduction Angiogenesis is fundamental for tumor growth and metastasis across many solid malignancies. Considerable interest has focused on the molecular regulation of tumor angiogenesis as a means to predict disease outcomes and guide therapeutic decisions. Methods In the present study, we investigated the prognostic value of transforming growth factor beta (TGF-β), epidermal growth factor (EGF), fibroblast growth factor (FGF), delta-like ligand 4 (DLL4), and vascular endothelial growth factor (VEGF) in the serum of 120 women diagnosed with breast cancer using ELISA as well as examined their associations with clinical parameters and the outcome of the disease. Results Our results demonstrated that the serum concentration of TGF-β and EGF were remarkably higher in patients with higher tumor size, end stages of the disease, and positive lymph node involvement compared to patients with lower tumor size, early stages of the disease, and negative lymph node involvement. In addition, we found a significant correlation between the serum concentration of VEGF and the level of EGF, FGF, and DLL4 in patients with breast cancer. Furthermore, both univariate and multivariate analyses showed that TGF-β and EGF can be used as end-stage predictors. Discussion/Conclusion Based on our findings, increasing the level of angiogenesis factors is significantly associated with higher tumor size and late stages of the disease in patients with breast cancer. Moreover, measuring the level of angiogenesis factors could lead to better prediction of disease outcomes and choosing the best treatments for patients.

Regulation of Angiogenesis by Non-Coding RNAs in Cancer.

Non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, have been identified as crucial regulators of various biological processes through epigenetic regulation, transcriptional regulation, and post-transcriptional regulation. Growing evidence suggests that dysregulation and activation of non-coding RNAs are closely associated with tumor angiogenesis, a process essential for tumor growth and metastasis and a major contributor to cancer-related mortality. Therefore, understanding the molecular mechanisms underlying tumor angiogenesis is of utmost importance. Numerous studies have documented the involvement of different types of non-coding RNAs in the regulation of angiogenesis. This review provides an overview of how non-coding RNAs regulate tumor angiogenesis. Additionally, we discuss emerging strategies that exploit non-coding RNAs for anti-angiogenic therapy in cancer treatment. Ultimately, this review underscores the crucial role played by non-coding RNAs in tumor angiogenesis and highlights their potential as therapeutic targets for anti-angiogenic interventions against cancer.

Regulation and Therapeutic Application of Long non-Coding RNA in Tumor Angiogenesis.

Tumor growth and metastasis rely on angiogenesis. In recent years, long non-coding RNAs have been shown to play an important role in regulating tumor angiogenesis. Here, we review the multidimensional modes and relevant molecular mechanisms of long non-coding RNAs in regulating tumor angiogenesis. In addition, we summarize new strategies for tumor anti-angiogenesis therapies by targeting long non-coding RNAs. The aim of this study is to provide new diagnostic targets and treatment strategies for anti-angiogenic tumor therapy.

LSD1 inhibition by tranylcypromine hydrochloride reduces alkali burn-induced corneal neovascularization and ferroptosis by suppressing HIF-1α pathway.

Corneal neovascularization (CNV) is a sight-threatening condition that necessitates epigenetic control. The role of lysine-specific demethylase 1 (LSD1) in CNV remains unclear, despite its established significance in tumor angiogenesis regulation. An alkali burn-induced CNV mouse model was used in vivo. The effects of LSD1 inhibitor tranylcypromine hydrochloride (TCP) were examined through slit lamp, histological staining, and immunofluorescence. The expression of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were assessed in corneal tissues. Oxidative stress and ferrous ion expression during CNV were determined using 4-HNE, GPX4, and FerroOrange staining. In vitro, a hypoxia-reoxygenation (H/R) model was established using human umbilical vein endothelial cells (HUVECs) to study LSD1 or hypoxia-inducible factor (HIF-1α) knockdown and lentiviral overexpression of HIF-1α. The effects on HUVECs migration, invasion, and angiogenesis were evaluated through cell scratching assay, transwell migration assay and tube formation assay. The role of ferroptosis was investigated using ROS staining, FerroOrange staining, and key ferroptosis proteins. Further, The JAK2/STAT3 pathway's involvement in CNV regulation was explored through in vivo experiments with subconjunctival injection of AG490. The results showed a substantial correlation between corneal damage and LSD1 levels. In addition, HIF-1α expression was also elevated after alkali burns, and subconjunctival injection of TCP reduced corneal inflammation and neovascularization. Corneal alkali burns increased ROS levels and reduced antioxidative stress indicators, accompanied by elevated ferrous ion levels, which were reversed by TCP injection. In vitro, TCP or siRNAs inhibited H/R-induced ferroptosis and angiogenesis in HUVECs by affecting specific protein expressions and MDA, SOD, and GSH levels. HIF-1α levels, associated with ROS production, ferroptosis, and angiogenesis, increased during H/R, but were reversed by TCP or siRNA administration. HIF-1α overexpression counteracted the effects of LSD1 inhibition. Additionally, AG490 injection effectively reduced HIF-1α and VEGFA expression in the CNV model. These findings suggest that LSD1 inhibition via the HIF-1α-driven pathway prevents angiogenesis, oxidative stress, and ferroptosis in corneal alkali burn-induced CNV, highlighting LSD1 as a potential therapeutic target.

Hypoxia-induced TMTC3 expression in esophageal squamous cell carcinoma potentiates tumor angiogenesis through Rho GTPase/STAT3/VEGFA pathway

BackgroundHypoxia is one of most typical features in the tumor microenvironment of solid tumor and an inducer of endoplasmic reticulum (ER) stress, and HIF-1α functions as a key transcription factor regulator to promote tumor angiogenesis in the adaptive response to hypoxia. Increasing evidence has suggested that hypoxia plays an important regulatory role of ER homeostasis. We previously identified TMTC3 as an ER stress mediator under nutrient-deficiency condition in esophageal squamous cell carcinoma (ESCC), but the molecular mechanism in hypoxia is still unclear.MethodsRNA sequencing data of TMTC3 knockdown cells and TCGA database were analyzed to determine the association of TMTC3 and hypoxia. Moreover, ChIP assay and dual-luciferase reporter assay were performed to detect the interaction of HIF-1α and TMTC3 promoter. In vitro and in vivo assays were used to investigate the function of TMTC3 in tumor angiogenesis. The molecular mechanism was determined using co-immunoprecipitation assays, immunofluorescence assays and western blot. The TMTC3 inhibitor was identified by high-throughput screening of FDA-approved drugs. The combination of TMTC3 inhibitor and cisplatin was conducted to confirm the efficiency in vitro and in vivo.ResultsThe expression of TMTC3 was remarkably increased under hypoxia and regulated by HIF-1α. Knockdown of TMTC3 inhibited the capability of tumor angiogenesis and ROS production in ESCC. Mechanistically, TMTC3 promoted the production of GTP through interacting with IMPDH2 Bateman domain. The activity of Rho GTPase/STAT3, regulated by cellular GTP levels, decreased in TMTC3 knockdown cells, whereas reversed by IMPDH2 overexpression. Additionally, TMTC3 regulated the expression of VEGFA through Rho GTPase/STAT3 pathway. Allopurinol inhibited the expression of TMTC3 and further reduced the phosphorylation and activation of STAT3 signaling pathway in a dose-dependent manner in ESCC. Additionally, the combination of allopurinol and cisplatin significantly inhibited the cell viability in vitro and tumor growth in vivo, comparing with single drug treatment, respectively.ConclusionsCollectively, our study clarified the molecular mechanism of TMTC3 in regulating tumor angiogenesis and highlighted the potential therapeutic combination of TMTC3 inhibitor and cisplatin, which proposed a promising strategy for the treatment of ESCC.

Angiopoietin4 (ANGPT4) expression and potential mechanisms in carcinogenesis: current achievements and perspectives.

Angiopoietin4(ANGPT4) which plays a significant role in endothelial cell proliferation, survival, angiogenesis and expansion in tumors and other pathological states is a significant regulator of tumor angiogenesis. ANGPT4 expression is enhanced in many cancer cells. For example, the overexpression of ANGPT4 promotes the formation, development and progress of lung adenocarcinoma, glioblastoma and ovarian cancer. Related studies show that ANGPT4 encourages the proliferation, survival and invasion of tumor cells, while promoting the expansion of the tumor vascular system and affecting the tumor immune microenvironment. ANGPT4 can also promote carcinogenesis by affecting the ERK1/2, PI3K/AKT and other signal pathways downstream of tyrosine kinase with immunoglobulin-like and EGF-like domains 2(TIE2) and TIE2. Therefore, ANGPT4 may be a potential and significant biomarker for predicting malignant tumor progression and adverse outcomes. In addition, inhibition of ANGPT4 may be a meaningful cancer treatment. This paper reviews the latest research results of ANGPT4 in preclinical research, and emphasizes its role in carcinogenesis. Additional research on the carcinogenic function of ANGPT4 could provide new insights into cancer biology and novel methods for cancer diagnosis and treatment.

Beta IV spectrin inhibits the metastatic growth of melanoma by suppressing VEGFR2-driven tumor angiogenesis.

Tumor-associated angiogenesis mediates the growth and metastasis of most solid cancers. Targeted therapies of the VEGF pathways can effectively block these processes but often fail to provide lasting benefits due to acquired resistance and complications. Recently, we discovered βIV -spectrin as a powerful regulator of angiogenesis and potential new target. We previously reported that βIV -spectrin is dynamically expressed in endothelial cells (EC) to induce VEGFR2 protein turnover during development. Here, we explored how βIV -spectrin influences the tumor vasculature using the murine B16 melanoma model and determined that loss of EC-specific βIV -spectrin dramatically promotes tumor growth and metastasis. Intraperitoneally injected B16 cells formed larger tumors with increased tumor vessel density and greater propensity for metastatic spread particularly to the chest cavity and lung compared to control mice. These results support βIV -spectrin as a key regulator of tumor angiogenesis and a viable vascular target in cancer.

In Silico and In Vitro Evaluation of Bevacizumab Biosimilar MB02 as an Antitumor Agent in Canine Mammary Carcinoma.

Canine mammary carcinomas (CMC) are associated with major aggressive clinical behavior and high mortality. The current standard of care is based on surgical resection, without an established effective treatment scheme, highlighting the urgent need to develop novel effective therapies. Vascular endothelial growth factor (VEGF) is a key regulator of tumor angiogenesis and progression in the majority of solid cancers, including human and canine mammary carcinomas. The first therapy developed to target VEGF was bevacizumab, a recombinant humanized monoclonal antibody, which has already been approved as an anticancer agent in several human cancers. The goal of this work was to establish the therapeutic value of MB02 bevacizumab biosimilar in CMC. First, through different in silico approaches using the MUSCLE multiple-sequence alignment tool and the FoldX protein design algorithm, we were able to predict that canine VEGF is recognized by bevacizumab, after showing an extremely high sequence similarity between canine and human VEGF. Further, by using an ELISA-based in vitro binding assay, we confirmed that MB02 biosimilar was able to recognize canine VEGF. Additionally, canine VEGF-induced microvascular endothelial cell proliferation was inhibited in a concentration-dependent manner by MB02 biosimilar. These encouraging results show a high potential for MB02 as a promising therapeutic agent for the management of CMC.

Neutrophils regulate tumor angiogenesis in oral squamous cell carcinoma and the role of Chemerin.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity. Tumor angiogenesis plays a crucial role in tumor progression. Studies have established the correlation between neutrophils and tumor angiogenesis in the tumor microenvironment. A previous study found that overexpression of Chemerin- in OSCC increased the infiltration of neutrophils in tumor tissues. This study aims to investigate the mechanisms underlying the regulation of the development and progression of OSCC, which have great significance in enhancing the postoperative survival of patients with OSCC. This study evaluated the accuracy of neutrophil count combined with MVD in predicting patients' survival time and its relationship with clinicopathological parameters and prognosis. Additionally, the study explored the effects of the Chemerin-neutrophil interaction on the angiogenic function of HUVECs. In OSCC, the overexpression of Chemerin promoted the angiogenesis of HUVECs through neutrophils. Moreover, Chemerin upregulated pro-angiogenic factors (e.g., VEGF-A, MMP-9, MMP-2, and S100A9) in neutrophils by activating MEK/ERK signaling pathway. In vivo experiments demonstrated that Chemerin may promote tumor growth by regulating tumor angiogenesis. In conclusion, the results suggest that neutrophil count and MVD serve as poor prognostic factors for patients with OSCC, and their combination is a more effective factor in predicting the survival time of OSCC patients. Neutrophils potentially contribute to angiogenesis through MEK/ERK signaling pathway via Chemerin and participate in the progression and metastasis of OSCC.

The Progress of Platelets in Breast Cancer.

Breast cancer is the most common female cancer and the sixth leading cause of death, seriously affecting the quality of life of women. Platelets, one of the fragments derived from megakaryocytes, are being increasingly investigated by tumor researchers because of their anticoagulant function. According to relevant studies, platelets, as the key source of circulating angiogenesis-related factors, can regulate tumor angiogenesis and vascular integrity, and they can also affect the tumor microenvironment, thereby facilitating the proliferation and differentiation of tumor cells. By covering or transferring normal MHC I molecules to tumor cells, platelets can protect tumor cells from being killed by the immune system and facilitate tumor cell metastasis. However, details on the mechanisms involved have remained elusive. This paper reviews and analyzes studies of the role of platelets in tumorigenesis, tumor cell proliferation, tumor metastasis, and cancer treatment to provide readers with a better understanding of the relevant studies.

The functional network of biglycan: A new frontier in tumor progression

AbstractBiglycan is a member of the small leucine‐rich proteoglycan family. Dysregulation of biglycan leads to a broad range of clinical consequences, such as osteoclastogenesis, inflammation, cardiovascular disease, and cancer. Biglycan binding to toll‐like receptor (TLR)−2 or TLR‐4 on immune cells lead to infiltration of immune cells to mediate the inflammatory response. Additionally, the extracellular matrix‐secreted soluble biglycan functions as a danger‐associated molecular pattern molecule involved in the induction of inflammation and cancer. High expression of biglycan is demonstrated in tumor endothelial cells (TECs) of various cancers and correlates with metastatic potential and poor clinical outcomes. This comprehensive review addresses the role of biglycan in both tumor cells and tumor stromal cells, especially TECs, in regulating tumor angiogenesis, tumor growth, metastasis, and chemotherapy resistance.